Cotrimoxazole (Trimethoprim-Sulfamethoxazole) Dosing and Treatment Guidelines
For most common bacterial infections, cotrimoxazole is dosed as 1 double-strength tablet (800mg/160mg sulfamethoxazole/trimethoprim) twice daily, with duration varying by indication from 3 days for uncomplicated cystitis to 14-21 days for severe infections like Pneumocystis pneumonia. 1, 2, 3
Standard Adult Dosing by Clinical Indication
Urinary Tract Infections
- Uncomplicated cystitis: 1 double-strength tablet twice daily for 3 days 1
- Pyelonephritis: 1 double-strength tablet twice daily for 14 days (only when pathogen confirmed susceptible) 1
- General UTI treatment: 1 double-strength tablet or 2 single-strength tablets (400mg/80mg) every 12 hours for 10-14 days 2, 3
Respiratory Infections
- Acute exacerbations of chronic bronchitis: 1 double-strength tablet twice daily for 14 days 2, 3
- Pneumocystis jirovecii pneumonia (treatment): 75-100 mg/kg/day sulfamethoxazole with 15-20 mg/kg/day trimethoprim divided every 6 hours for 14-21 days 4, 1, 2, 3
- PCP prophylaxis: 1 double-strength tablet daily (preferred) or 1 single-strength tablet daily or 1 double-strength tablet three times weekly 4
Gastrointestinal Infections
- Shigellosis: Same dosing as UTI (1 double-strength tablet twice daily) but for only 5 days 2, 3
- Traveler's diarrhea: 1 double-strength tablet twice daily for 5 days 4, 2, 3
Skin and Soft Tissue Infections (Including MRSA)
- Standard dosing: 1-2 double-strength tablets twice daily for 7-10 days 1
Pediatric Dosing (Children ≥2 Months)
General Infections
- Standard dose: 40 mg/kg/day sulfamethoxazole with 8 mg/kg/day trimethoprim divided every 12 hours 2, 3
- UTI and acute otitis media: Same standard dose for 10 days 2, 3
- Shigellosis: Same standard dose for 5 days 2, 3
Pneumocystis Pneumonia
- Treatment: 75-100 mg/kg/day sulfamethoxazole with 15-20 mg/kg/day trimethoprim divided every 6 hours for 14-21 days 4, 2, 3
- Prophylaxis: 750 mg/m²/day sulfamethoxazole with 150 mg/m²/day trimethoprim divided twice daily on 3 consecutive days per week (maximum 1600mg/320mg daily) 2, 3
Prophylactic Dosing
UTI Prevention
- Daily prophylaxis: 40mg trimethoprim/200mg sulfamethoxazole (half single-strength tablet) once daily 5
- Alternative regimen: 40mg/200mg three times weekly 5
- Postcoital prophylaxis: 40mg/200mg or 80mg/400mg (single-strength tablet) once after intercourse 5
- Critical caveat: Only use when local E. coli resistance rates are <20% 5
PCP Prophylaxis in HIV/Immunocompromised
- Adults: 1 double-strength tablet daily (provides cross-protection against toxoplasmosis and respiratory bacterial infections) 4
- Alternative: 1 single-strength tablet daily or 1 double-strength tablet three times weekly 4
Post-Transplant Prophylaxis
- Kidney transplant recipients: Daily TMP-SMX for at least 6 months post-transplant 5
Renal Dose Adjustment
Dosing must be reduced in renal impairment 2, 3:
- CrCl >30 mL/min: Standard dosing
- CrCl 15-30 mL/min: 50% of usual dose
- CrCl <15 mL/min: Use not recommended
Critical Contraindications and Precautions
Absolute Contraindications
- Infants <2 months of age: Risk of kernicterus 4, 2, 3
- Third trimester pregnancy: Increased risk of birth defects and kernicterus 1
- Nursing mothers: Kernicterus risk in infant 1
Monitoring Requirements
- Hematologic surveillance: Complete blood counts with differential and platelets at initiation and monthly intervals to assess for bone marrow suppression 5
- Watch for serious reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, interstitial nephritis 1
Antimicrobial Spectrum and Clinical Context
Cotrimoxazole provides broad-spectrum coverage against both Gram-positive and Gram-negative aerobic bacteria, including community-acquired MRSA 1. The combination is effective against Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, and common urinary pathogens 1.
When Cotrimoxazole is Superior to Trimethoprim Alone
The combination is specifically indicated for 6:
- Pneumocystis jirovecii pneumonia
- Toxoplasmosis
- Nocardiosis
- Brucellosis
- Chancroid
When Trimethoprim Alone May Suffice
For many common respiratory and urinary tract infections, trimethoprim alone (without sulfamethoxazole) is equally effective with fewer adverse effects 7, 6. However, the fixed-dose combination remains standard in most clinical practice 1, 2, 3.
Common Pitfalls to Avoid
- Resistance patterns: Increasing bacterial resistance is compromising cotrimoxazole's utility, particularly for empiric treatment of traveler's diarrhea where quinolones are now preferred first-line 4
- Desensitization option: For patients with non-life-threatening adverse reactions (especially fever and rash), gradual reintroduction with dose escalation allows up to 70% to tolerate the drug 4
- Avoid empiric use in high-resistance areas: Do not use for UTI prophylaxis when local resistance exceeds 20% 5
- Consider non-antibiotic alternatives first: For recurrent UTI prevention, try cranberry products, methenamine hippurate, vaginal estrogen, or increased water intake before committing to antibiotic prophylaxis 5